Orphanet J Rare Dis. 2026 Jan 20;21(1):21. doi: 10.1186/s13023-025-04168-3.
ABSTRACT
BACKGROUND: Fabry disease (FD) is a multisystemic, progressive, X-linked genetic disorder caused by dysfunction of the enzyme α-galactosidase A. Symptoms commonly present in childhood in classic patients. Prior studies in classic patients suggest primary presenting features include gastrointestinal (GI) symptoms such as abdominal pain, bloating, and diarrhea. In this longitudinal study, we collected annual questionnaires and medical records from families of 29 children between 3 months and 9.5 years old, including the Rome III questionnaire. We compared symptom detection of abdominal pain, constipation, diarrhea, and bloating via three methods: the Rome III, a simple review of symptoms questionnaire, and pediatrician notes including a review of systems.
RESULTS: Both questionnaires elicited all GI symptoms more frequently than pediatrician notes (log rank test, p < 0.001). The two questionnaires had weaker agreement for constipation than other symptoms (per kappa statistic) and more similar detection at a younger age. After 24 months, the Rome III outperformed the simple review of symptoms questionnaire (Fisher's exact test, p < 0.001). Pediatrician notes never recorded bloating or severe episodes of abdominal pain.
CONCLUSIONS: Targeted questionnaires elicit early gastrointestinal symptoms in pediatric Fabry disease patients that would otherwise go unnoticed at a standard doctor's appointment. Based on manual analysis of questionnaire data, a list of questions is suggested to support pediatricians of young patients with FD in recognizing GI symptoms. Use of more targeted and specific questions regarding GI symptoms is warranted in pediatric appointments of patients with FD, with age-appropriate expansion of the questions at 24 months of age. Early detection of symptoms in this population is critical as individual treatment plans are based on symptom onset and as newborn screening is expanding.
PMID:41559791 | PMC:PMC12821958 | DOI:10.1186/s13023-025-04168-3